:Cannabigerol

{{more sources|section|date=December 2024}}

In vitro, CBG has identified pharmacodynamic actions and its mechanism of action appears to be from interactions with multiple targets.

CBG is a weak ligand of the cannabinoid CB₁ and CB₂ receptors with affinities (K_i) of 380–2,600{{nbsp}}nM and 153–3,460{{nbsp}}nM, respectively.{{cite journal | vauthors = Sampson PB | title = Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two" | journal = J Nat Prod | volume = 84 | issue = 1 | pages = 142–160 | date = January 2021 | pmid = 33356248 | doi = 10.1021/acs.jnatprod.0c00965 | bibcode = 2021JNAtP..84..142S | url = }}{{cite web | last=Liu | first=Tiqing | title=BindingDB BDBM50318487 CHEMBL497318::Cannabigerol | website=BindingDB | url=https://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50318487 | access-date=14 August 2024}} It is a weak partial agonist or antagonist of both of these receptors. There is no information on the binding or activity of CBG at the GPR55 (the potential non-homologous CB₃ receptor). CBG has relatively low affinity for the cannabinoid receptors, with approximately 5-fold lower affinity for the CB₁ receptor and 27-fold lower affinity for the CB₂ receptor than THC.{{cn|date=December 2024}}

CBG is a highly potent agonist of the α₂-adrenergic receptor ({{Abbrlink|EC₅₀|half-maximal effective concentration}} = 0.2–72.8{{nbsp}}nM) and a moderately potent antagonist of the serotonin 5-HT_1A receptor (K_B = 51.9{{nbsp}}nM).{{cite journal | vauthors = Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG | title = Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist | journal = Br J Pharmacol | volume = 159 | issue = 1 | pages = 129–141 | date = January 2010 | pmid = 20002104 | pmc = 2823359 | doi = 10.1111/j.1476-5381.2009.00515.x | url = }} Activation of the α₂-adrenergic receptor by CBG might produce effects including sedation, dry mouth, and decreased heart rate and blood pressure. This has raised safety concerns about CBG. The actions of CBG at the α₂-adrenergic receptor and 5-HT_1A receptor are of far greater potency than its interactions with the cannabinoid receptors and are more likely to be involved in its pharmacodynamic effects.{{cn|date=December 2024}}

The compound is a weak agonist of the transient receptor potential channels TRPA1 ({{Abbr|EC₅₀|half-maximal effective concentration}} = 700{{nbsp}}nM), TRPV1 ({{Abbr|EC₅₀|half-maximal effective concentration}} = 1,300{{nbsp}}nM), TRPV2 ({{Abbr|EC₅₀|half-maximal effective concentration}} = 1,720{{nbsp}}nM), TRPV3 ({{Abbr|EC₅₀|half-maximal effective concentration}} = 1,000{{nbsp}}nM), and TRPV4 ({{Abbr|EC₅₀|half-maximal effective concentration}} = 5,100{{nbsp}}nM) (efficacy 18–100% at these targets) and a more potent antagonist of the transient receptor potential channel TRPM8 ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} = 160{{nbsp}}nM). It is also a weak agonist of the peroxisome proliferator-activated receptor PPAR-γ ({{Abbr|EC₅₀|half-maximal effective concentration}} = 1,270–15,700{{nbsp}}nM).

CBG is a voltage-gated sodium channel (VGSC) blocker (Na_v1.1, Na_v1.2, Na_v1.5, and Na_v1.7) and voltage-dependent calcium channel (VDCC) blocker.{{cite journal | vauthors = Ghovanloo MR, Estacion M, Higerd-Rusli GP, Zhao P, Dib-Hajj S, Waxman SG | title = Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability | journal = Br J Pharmacol | volume = 179 | issue = 15 | pages = 4010–4030 | date = August 2022 | pmid = 35297036 | doi = 10.1111/bph.15833 | url = }} Inhibition of VGSCs may be involved in the analgesic effects of CBG.

It shows no inhibition of several endocannabinoid-metabolizing enzymes including fatty acid amide hydrolase (FAAH), diacylglycerol lipase (DGL), and N-acylethanolamine acid amide hydrolase (NAAA). However, other research has found that CBG does inhibit FAAH and DGL, as well as monoacylglycerol lipase (MAGL), although it is less potent as an inhibitor of FAAH than cannabidiol (CBD). Aside from endocannabinoid-metabolizing enzymes, CBG is a weak inhibitor of the cyclooxygenase COX-1 and COX-2 enzymes (30% inhibition of each at 25,000{{nbsp}}nM). In addition, it has been found to inhibit both the metabolism and reuptake of anandamide.

The pharmacokinetics of CBG have been studied in animals and to a lesser extent in humans. CBG is metabolized in the liver by CYP2J2, similarly to other cannabinoids as well as endocannabinoids.

CBG is a highly lipophilic and hydrophobic compound. Its predicted log P ranges from 7.0 to 7.5.{{cite web | title=Cannabigerol: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=1 February 2019 | url=https://go.drugbank.com/drugs/DB14734 | access-date=14 August 2024}}{{cite web | title=Cannabigerol | website=ChemSpider | date=14 August 2024 | url=https://www.chemspider.com/Chemical-Structure.4474921.html | access-date=14 August 2024}}

Synthetic derivatives of CBG have been synthesized and studied.

CBG was isolated from cannabis in 1964.

CBG is not scheduled by the United Nations Convention on Psychotropic Substances.{{citation needed|date=April 2018}} In the United States, CBG derived from marijuana is illegal under the Controlled Substances Act, while CBG derived from hemp is legal, as long as the hemp THC content is less than 0.3% of dry weight.{{cite web |title=FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD) |url=https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd |archive-url=https://web.archive.org/web/20191001002132/https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd |url-status=dead |archive-date=October 1, 2019 |publisher=US Food and Drug Administration |access-date=7 July 2022 |date=21 January 2021}}{{Cite web|url=https://www.gpo.gov/fdsys/pkg/USCODE-2016-title21/pdf/USCODE-2016-title21-chap13-subchapI-partA-sec802.pdf|title=USC > Title 21 > Chapter 13 > Subchapter I > Part A > § 802. Definitions: (16)|date=2016|website=Government Publishing Office - US Code}}

In Switzerland, it is legal to produce hemp rich in CBG as a tobacco substitute, as long as its THC content remains below 1.0%.{{Cite news |last=BAG |first=Bundesamt für Gesundheit |title=Häufig gestellte Fragen (FAQ) zu Tabakersatzprodukten mit THC-armem Hanf mit CBD |url=https://www.bag.admin.ch/bag/de/home/gesetze-und-bewilligungen/gesuche-bewilligungen/gesuche-bewilligungen-im-bereich-sucht/gesetzliche-vorgaben-tabakprodukte/faq-cbd.html |access-date=2022-07-06 |website=www.bag.admin.ch |language=de |archive-date=2023-09-25 |archive-url=https://web.archive.org/web/20230925084028/https://www.bag.admin.ch/bag/de/home/gesetze-und-bewilligungen/gesuche-bewilligungen/gesuche-bewilligungen-im-bereich-sucht/gesetzliche-vorgaben-tabakprodukte/faq-cbd.html |url-status=dead }}

As of 2022, the US Food and Drug Administration has issued numerous warning letters to American companies for illegally marketing cannabis supplement products, including one selling CBG products with unproven illegal claims of efficacy against the COVID-19 virus and inflammation.{{cite web | vauthors = Ashley D |date=28 March 2022 |title=Warning Letter to Greenway Herbal Products LLC; Ref. 627042 |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/greenway-herbal-products-llc-627042-03282022 |access-date=7 July 2022 |publisher=Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration}}

File:Biosynthesis of cannabigerol.jpg

The biosynthesis of CBG begins by loading hexanoyl-CoA onto a polyketide synthase assembly protein and subsequent condensation with three molecules of malonyl-CoA.{{cite journal | vauthors = Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE | title = Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 31 | pages = 12811–12816 | date = July 2012 | pmid = 22802619 | pmc = 3411943 | doi = 10.1073/pnas.1200330109 | doi-access = free | bibcode = 2012PNAS..10912811G }} This polyketide is cyclized to olivetolic acid via olivetolic acid cyclase, and then prenylated with a ten carbon isoprenoid precursor, geranyl pyrophosphate, using an aromatic prenyltransferase enzyme, geranyl-pyrophosphate—olivetolic acid geranyltransferase, to biosynthesize cannabigerolic acid, which can then be decarboxylated to yield CBG.

CBG is under laboratory research to determine its pharmacological properties and potential effects in disease conditions, with no conclusions about therapeutic effects or safety, as of 2021.{{cite book |title=Phytocannabinoids |vauthors=Morales P, Hurst DP, Reggio PH |year=2017 |isbn=978-3-319-45539-6 |series=Progress in the Chemistry of Organic Natural Products |volume=103 |pages=103–131 |chapter=Molecular Targets of the Phytocannabinoids: A Complex Picture |doi=10.1007/978-3-319-45541-9_4 |pmc=5345356 |pmid=28120232}}{{cite journal |vauthors=Couch DG, Maudslay H, Doleman B, Lund JN, O'Sullivan SE |date=March 2018 |title=The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis |journal=Inflammatory Bowel Diseases |volume=24 |issue=4 |pages=680–697 |doi=10.1093/ibd/izy014 |pmid=29562280 |doi-access=free}} A clinical trial published in July 2024 assessed the effects of CBG on anxiety, stress, and mood.{{cite journal | vauthors = Cuttler C, Stueber A, Cooper ZD, Russo E | title = Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial | journal = Sci Rep | volume = 14 | issue = 1 | pages = 16163 | date = July 2024 | pmid = 39003387 | pmc = 11246434 | doi = 10.1038/s41598-024-66879-0 | bibcode = 2024NatSR..1416163C | url = }}{{cite web | title=Cannabigerol (CBG) Reduces Anxiety and Improves Memory | website=Neuroscience News | date=31 July 2024 | url=https://neurosciencenews.com/cbg-anxiety-memory-27507/ | access-date=14 August 2024}}

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Category:5-HT1A antagonists

Category:Alpha-2 adrenergic receptor agonists

Category:Calcium channel blockers

Category:CB1 receptor antagonists

Category:Phytocannabinoids

Category:Resorcinols

Category:Terpeno-phenolic compounds

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Category:Drugs with unknown mechanisms of action